Cardiovascular Disease
Cardiovascular disease refers to the class of diseases that involve the heart or blood vessels (arteries and veins). While the term technically refers to any disease that affects the cardiovascular system (as used in MeSH), it is usually used to refer to those related to atherosclerosis (arterial disease). These conditions have similar causes, mechanisms, and treatments. In practice, cardiovascular disease is treated by cardiologists, thoracic surgeons, vascular surgeons, neurologists, and interventional radiologists, depending on the organ system that is being treated. There is considerable overlap in the specialties, and it is common for certain procedures to be performed by different types of specialists in the same hospital.
Most Western countries face high and increasing rates of cardiovascular disease. Each year, heart disease kills more Americans than cancer [2]. Diseases of the heart alone caused 30% of all deaths, with other diseases of the cardiovascular system causing substantial further death and disability. Two out of three cardiac deaths occur without any diagnosis of cardiovascular disease [3]. Up until the year 2008, it was the major cause of death and disability in the United States and most European countries. A large histological study (PDAY) showed vascular injury accumulates from adolescence, making primary prevention efforts necessary from childhood [4] [5].
In contrast with gradual built-up of vessel narrowing, the major cause of heart attack (Acute Myocardial Infarction—AMI) or stroke is vulnerable (atherosclerotic) plaques. A vulnerable plaque is an athermatous plaque, an unstable collection of white blood cells (primarily macrophages) and lipids (including cholesterol) in the wall of an artery which is particularly prone to rupture, producing sudden vessel blockage and major problems, such as a heart attack. Researchers have found that inflammation in the arteries leads to the development of “soft” or vulnerable plaque, which when released aggressively promotes blood clotting. When this inflammation is combined with other stresses, such as high blood pressure (increased mechanical stretching and contraction of the arteries with each heart beat), it can cause the thin covering over the plaque to split, spilling the contents of the vulnerable plaque into the bloodstream. The sticky cytokines on the artery wall capture blood cells (mainly platelets) that accumulate at the site of injury. When these cells clump together, they form a clot, sometimes large enough to block the artery. The most frequent cause of a cardiac event following rupture of a vulnerable plaque is blood clotting on top of the site of the ruptured plaque that blocks the lumen of the artery, thereby stopping blood flow to the tissues the artery supplies.
By the time that heart problems are detected, the underlying cause (atherosclerosis) is usually quite advanced, having progressed for decades. There is therefore increased emphasis on preventing atherosclerosis by modifying risk factors, such as healthy eating, exercise and avoidance of smoking. Established cardiovascular risk factors, including dyslipidemia, smoking, hypertension, and diabetes mellitus, have been incorporated into algorithms for risk assessment in the general population [1], [2] but these characteristics do not fully explain cardiovascular risk [3], [4], [5] and other factors are sought.
Biomarkers
A biomarker is a substance or measurement that indicates important facts about a living organism, usually a patient. It is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. In other words, biomarkers can provide the physician with useful information about:                1. Biologic state of an individual;        2. Disease risk;        3. Disease diagnosis;        4. Disease progression;        5. Treatments of choice;        6. Monitoring responses to treatment;        7. Endpoints for assessing treatment efficacy.        
Biomarkers thus allow the physician a preventive or therapeutic jump on the individual's disease process.
An effective biomarker, as a high concentration of “bad” cholesterol, for example, can inform us about associated complexities related to genes, heredity, metabolism, diet, blood vessel walls, and the risks of vascular embolism and occlusion [3]. The biomarker, in short, reflects and summarizes all the agents and processes that are needed to produce it—however many and complex these agents and processes may be. A simple biomarker is informative when it faithfully signifies for us the complex factors from which the biomarker emerges.
There is thus substantial interest in the use of newer biomarkers to identify persons who are at risk for the development of cardiovascular disease and who could be targeted for preventive measures. Some biomarkers are thought to offer a more detailed risk of cardiovascular disease. However, the clinical value of these biomarkers is questionable [6]. Many individual biomarkers have been related to cardiovascular risk in ambulatory persons, including levels of C-reactive protein [7], [8], B-type natriuretic peptide [9], fibrinogen [10], D-dimer [11] and homocysteine [12]. Measurement of several biomarkers simultaneously (the “multimarker” approach) could enhance risk stratification of ambulatory persons. This approach was tried by Wang et al. (NEJM v.355.2631-2639), by testing the usefulness of 10 previously reported biomarkers for predicting death and major cardiovascular events in a large population. However, the results were unpromising.
Currently, biomarkers which may reflect a higher risk of cardiovascular disease include:
Higher fibrinogen and PAI-1 blood concentrations;
Elevated homocysteine, or even upper half of normal;
Elevated blood levels of asymmetric dimethylarginine;
High inflammation as measured by C-reactive protein; and,
Elevated blood levels of Brain Natriuretic Peptide (also known as B-type) (BNP) [7].
A fairly recent emphasis is on the link between low-grade inflammation that hallmarks atherosclerosis and its possible interventions. C-reactive protein (CRP) is an inflammatory marker that may be present in increased levels in the blood in patients at risk for cardiovascular disease. Its exact role in predicting disease is the subject of debate.
In light of the above, it is clear that a long felt and unmet need exists for a reliable method of identifying at a very early stage, the beginning of a cardiovascular disease in an individual. Such a method would make it possible to act quickly without having to wait for real-time events to take place. For example, anticipating, treating and monitoring the state of the individual would improve the ability to prevent a future heart attack or an impending stroke event.